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1.
Experimental & Molecular Medicine ; : e10-2013.
Artículo en Inglés | WPRIM | ID: wpr-199830

RESUMEN

Human mesenchymal stem cells (MSCs) have emerged as attractive cellular vehicles to deliver therapeutic genes for ex-vivo therapy of diverse diseases; this is, in part, because they have the capability to migrate into tumor or lesion sites. Previously, we showed that MSCs could be utilized to deliver a bacterial cytosine deaminase (CD) suicide gene to brain tumors. Here we assessed whether transduction with a retroviral vector encoding CD gene altered the stem cell property of MSCs. MSCs were transduced at passage 1 and cultivated up to passage 11. We found that proliferation and differentiation potentials, chromosomal stability and surface antigenicity of MSCs were not altered by retroviral transduction. The results indicate that retroviral vectors can be safely utilized for delivery of suicide genes to MSCs for ex-vivo therapy. We also found that a single retroviral transduction was sufficient for sustainable expression up to passage 10. The persistent expression of the transduced gene indicates that transduced MSCs provide a tractable and manageable approach for potential use in allogeneic transplantation.


Asunto(s)
Adolescente , Animales , Niño , Humanos , Ratones , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Transformación Celular Neoplásica/efectos de los fármacos , Citosina Desaminasa/genética , Fluorouracilo/farmacología , Terapia Genética , Inestabilidad Genómica/efectos de los fármacos , Cariotipo , Células Madre Mesenquimatosas/citología , Células Madre Multipotentes/citología , Neoplasias/terapia , Retroviridae/metabolismo , Factores de Tiempo , Transducción Genética
2.
Experimental & Molecular Medicine ; : 43-51, 2004.
Artículo en Inglés | WPRIM | ID: wpr-190975

RESUMEN

Enzyme/prodrug approach is one of the actively developing areas for cancer therapy. In an effort to develop more effective enzyme/prodrug systems, cell-permeable cytosine deaminase was produced by fusing yeast cytosine deaminase (yCD) in frame with RKKRRQRRR domain of HIV-1 Tat which is an efficient delivery peptide of the foreign proteins into cells. The purified Tat-yCD fusion protein expressed in Escherichia coli was readily transduced into mammalian cells in a time- and dose-dependent manner. A significant level of the transduced Tat-yCD protein was recovered in the cell and was stable for 24 h as indicated by both results of the enzymatic assay of 5-fluorocytosine (5-FC) conversion to 5-fluorouracil (5-FU) and Western blot analysis. The cells transduced with Tat-yCD become highly sensitive to the cytotoxicity of 5-FC, while cells treated with yCD are unaffected by 5-FC. In addition, a strong bystander effect was observed with conditioned media from cells transduced with Tat-yCD added to non-transduced cells. Tat-yCD fusion protein demonstrated here for its ability to transduce into cells and convert nontoxic prodrug 5-FC to the toxic antimetabolite 5-FU, may be a useful approach for cancer therapy.


Asunto(s)
Animales , Humanos , Antimetabolitos/metabolismo , Efecto Espectador , Citosina Desaminasa/genética , Flucitosina/metabolismo , Productos del Gen tat/química , Vectores Genéticos/genética , VIH-1/metabolismo , Células HeLa/efectos de los fármacos , Profármacos/metabolismo , Proteínas Recombinantes de Fusión/genética , Proteínas de Saccharomyces cerevisiae/genética , Transducción Genética
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